Supplementary Material for: Impact of Renin-Angiotensin System Blockade on Mortality and Allograft Loss among Renal Transplant Recipients: A Systematic Review and Meta-Analysis

Introduction:The blockade of the renin-angiotensin system (RAS) has a beneficial effect on reducing the levels of proteinuria and blood pressure in patients with chronic kidney disease (CKD) and reduces the risk of developing end-stage kidney disease (ESKD) in CKD patients. Nonetheless, a debate persists regarding the impact of RAS inhibitors on outcomes such as mortality and graft survival in renal transplant patients. To assess the effect of RAS inhibitors on graft recipients in the past decade, we conducted a systematic review and meta-analysis. Methods: We searched Embase, PubMed, and the Cochrane Central Register of Clinical Trials from January 1, 2012, to August 1, 2022. We included 14 articles, comprising 5 randomized controlled trials (RCTs) and 9 cohort studies, including 45,377 patients. These studies compared patient or graft survival between an RAS inhibitors treatment arm and a control arm. Results: The meta-analysis revealed that RAS blockade was significantly associated with lower mortality in cohort studies (risk ratio [RR] = 0.66, 95% confidence interval [CI]: 0.55-0.79), reduced allograft loss in cohort studies (RR = 0.62, 95% CI: 0.54-0.71), and significant changes in systolic blood pressure in RCTs. Subgroup analysis of the groups of interest (interventions involving RAS blockade, follow-up period of ≥ 5 years) showed consistently reduced mortality (RR = 0.67, 95% CI: 0.56-0.81) and reduced allograft loss (RR = 0.61, 95% CI: 0.54-0.70). Conclusions: Our results demonstrated that the application of RAS blockade among renal transplant recipients was associated with lower mortality and allograft loss in cohort studies but not in RCTs. More powered clinical trials are needed to evaluate the effects of RAS blockade in renal transplant recipients.